A retrospective analysis has shown that increasing the dose of subcutaneous infliximab (CT-P13 SC) from 120 to 240 mg Q2W in patients with inflammatory bowel disease who initially responded but subsequently lost response leads to improved clinical efficacy over an extended period.

Study participants were individuals with moderate-to-severe active Crohn’s disease (CD) and ulcerative colitis (UC) from the LIBERTY-CD and LIBERTY-UC studies. IV infliximab (CT-P13 IV) 5 mg/kg was given as induction therapy at weeks 0, 2, and 6. By week 10, clinical responders were randomized 2:1 to receive CT-P13 SC 120 mg or placebo Q2W as maintenance therapy up to week 54. [CCC 2025, abstract P037]

The open-label extension (OLE) phase ensued thereafter (week 54?102), with participants continuing to receive their assigned treatments. During this phase, the experimental arm included 192 CD patients (median age 36 years, 58.4 percent men) and 237 UC patients (median age 37 years, 57.4 percent men). Of these, 42 and 71, respectively, met the loss of response criteria* and were allowed to up their dose to 240 mg Q2W from week 22 through 102.

By week 102, dose escalation led to improved efficacy in both CD and UC subgroups, as reflected by the proportion of participants who achieved clinical remission (71.4 percent and 35.2 percent, respectively) and clinical response (69 percent and 60.6 percent).

To further put this into context, prior to dose escalation, the percentages of participants who have achieved clinical remission were only 2 percent and 7 percent in the respective CD and UC subsets; for clinical response, the corresponding rates were 29 percent and 39 percent.

“[Moreover, the] response after dose escalation was fast, with most patients regaining response within 8 weeks,” the researchers said. The fractions of participants achieving clinical remission/response 8 weeks post-dose escalation were 74 percent and 82 percent in the CD subgroup and 43 percent and 91 percent in the UC subset.

The CDAI** and PMS*** scores also dropped in both CD and UC subgroups 8 weeks after dose escalation, which was sustained through study week 102.

“The multiple logistic regression analysis with demographic variables as covariates showed that clinical remission at week 10 has a significant association with clinical remission at week 102 in patients who had dose escalation (p=0.0395 [CD] and p=0.0356 [UC]),” said the investigators.

In the pooled analysis of the CD and UC subgroups, there was no significant difference between those who did and did not escalate their dose, as evidenced by the incidence of treatment-emergent adverse events (AEs; 85.2 percent vs 78.8 percent), treatment-emergent serious AEs (13 percent vs 10.5 percent), systemic injection reaction (4.3 percent vs 2.8 percent), localized injection site reaction (8.7 percent vs 5.8 percent), infections (45.2 percent vs 43.4 percent), and positive conversion in antidrug antibody (71.3 percent vs 73.2 percent).

“[Taken together,] the findings suggest that dose escalation of CT-P13 SC from 120 mg to 240 mg Q2W [is] effective in restoring efficacy over an extended period of 102 weeks,” said the researchers.

The safety profiles, including the immunogenicity results, were generally comparable between patients who did and did not have dose escalation, with no new safety concerns following dose escalation, they added.

*CD: CDAI score increase of ≥100 points from week 10 (total score ≥220); UC: Modified Mayo score (MMS) increase of ≥2 points and ≥30 percent from week 10, with actual value of ≥5 points, and endoscopic subscore of ≥2 points

**CDAI: Crohn’s Disease Activity Index

***PMS: Partial Mayo score